creators_name: Andrianifahanana, Mahefatiana
creators_name: Singh, A P
creators_name: Nemos, C
creators_name: Ponnusamy, M P
creators_name: Moniaux, N
creators_name: Mehta, P P
creators_name: Varshney, Grish C
creators_name: Batra, S K
type: article
datestamp: 2012-02-17 16:39:42
lastmod: 2015-01-07 05:35:22
metadata_visibility: show
title: IFN-gamma-induced expression of MUC4 in pancreatic cancer cells is mediated by STAT-1 upregulation: a novel mechanism for IFN-gamma response.
ispublished: pub
subjects: QR
full_text_status: restricted
note: Copyright of this article belongs to Nature Publihsing Group.
abstract: MUC4 is a transmembrane mucin, which is aberrantly expressed in pancreatic adenocarcinoma with no detectable expression in the normal pancreas. Here, we present a novel mechanism of IFN-gamma-induced expression of MUC4 in pancreatic cancer cells. Our studies highlight the upregulation of STAT-1 as a basis for MUC4 induction and demonstrate that its activation and upregulation by IFN-gamma are two distinct, albeit temporally integrated, signalling events that drive the selective induction of IRF-1 and MUC4, respectively, within a single cell system. The profile of interferon regulatory factor (IRF)-1 gene induction by IFN-gamma is consistent with its rapid transactivation by phospho-Y701-STAT-1. In contrast, the induction of the MUC4 mucin gene expression is relatively delayed, and occurs only in response to an increase in STAT-1 expression. A progressive binding of STAT-1 to various gamma-interferon-activated sequences (GAS) in the MUC4 promoter is observed in chromatin immunoprecipitation assay, indicating its direct association. Stimulation of STAT-1 expression by double-stranded polynucleotides or ectopic expression is shown to induce MUC4 expression, without Y701 phosphorylation of STAT-1. This effect is abrogated by short interfering RNA (siRNA)-mediated inhibition of STAT-1 expression, supporting further the relevance of STAT-1 in MUC4 regulation. In conclusion, our findings identify a novel mechanism for MUC4 regulation in pancreatic cancer cells and unfold new perspectives on the foundation of IFN-gamma-dependent gene regulation.
date: 2007-11-08
date_type: published
publication: Oncogene
volume: 26
number: 51
publisher: Nature Publishing Group
pagerange: 7251-61
refereed: TRUE
issn: 0950-9232
official_url: http://www.nature.com/onc/journal/v26/n51/pdf/1210532a.pdf
related_url_url: http://www.nature.com/onc/journal/v26/n51/pdf/1210532a.pdf
related_url_type: pub
citation:   Andrianifahanana, Mahefatiana and Singh, A P and Nemos, C and Ponnusamy, M P and Moniaux, N and Mehta, P P and Varshney, Grish C and Batra, S K  (2007) IFN-gamma-induced expression of MUC4 in pancreatic cancer cells is mediated by STAT-1 upregulation: a novel mechanism for IFN-gamma response.  Oncogene, 26 (51).  pp. 7251-61.  ISSN 0950-9232     
document_url: http://crdd.osdd.net/open/1048/1/varshney2007.pdf